Emergence of antimicrobial resistance is an ever-increasing threat to our ability to treat a wide range of infections caused by microbes that thwart or block antimicrobial therapy. Staphylococcus aureus, an organism that is frequently found to be resistant to multiple antibiotics, is a major and increasing cause of morbidity and mortality in patients on chronic dialysis. Since nasal carriage of Staphylococcus aureus generally precedes infection and is a well established risk factor for invasive disease, eradication of this organism from the nares is of major clinical importance. Current strategies, particularly those that use antibiotics, often lead to antimicrobial resistance, side effects and relapse. Probiotics, particularly Lactobacillus GG (LGG) are capable of killing various bacteria, including Staphylococcus aureus, in vitro, by a variety of mechanisms. Preliminary data from one small study in healthy volunteers suggests that LGG may be able to eradicate nasal carriage of S aureus. We propose to conduct a pilot double-blind randomized placebo controlled clinical trial to refine methodology and determine the feasibility of evaluating whether LGG administered orally or topically is effective in eliminating nasal colonization with Staphylococcus aureus in patients on chronic hemodialysis. If safe and effective, LGG may provide an alternative way to eliminate this bacteria without use of antimicrobials that risk emergence of resistance. Fifty patients on hemodialysis will be recruited into the study, 20 will receive oral LGG, 20 will receive topical LGG and 10 will receive oral and topical placebo. The specific aims are to: (1) refine and test feasibility of administering oral and topical probiotics and matching placebo, in preparation for future studies that will investigate the effect of probiotics on eradication of nasal carriage of Staphylococcus aureus; (2) collect pilot data on limination of nasal colonization with Staphyloccous aureus to power future studies that will evaluate whether LGG is an effective alternative to antimicrobials; and (3) determine whether LGG colonizes the nares as a first step to exploring potential mechanisms by which LGG may influence mucosal Staphylococcus aureus colonization. This study has the potential to provide insight into a novel alternative approach to eradicate and prevent the spread of antimicrobial resistant pathogens. [unreadable] [unreadable] [unreadable]